Elimination of secretions from the lung is important in the pathogenesis and treatment of many respiratory problems. Inhaled particlates and noxious gases are largely removed from the inspired air within the tracheobronchial tree. Thus it is necessary to understand the physiology of pulmonary mucociliary transport and to develop improved methods to measure its response to drugs, disease and inhaled toxicants. This proposal is concerned with the development and application of new methodology to measure mucociliary clearance from specific regions of the human tracheobronchial tree, i.e., small airways, large airways and the trachea. The first section of the study is designed to develop the optimum aerosol deposition patterns for studying clearance from these regions. Deposition studies will be carried out in hollow casts made from human lungs. Initial in vivo studies will determine the effect of xylocaine, particle size and mucus volume on mucociliary tracheal transport rates. Most of the human clearance studies will measure regional clearance in a healthy nonsmoking population, together with the long term variation of transport rates in these regions. Drugs which affect the autonomic nervous system, namely, methacholine bromide, atropine sulfate, metaproterenol and propranolol hydrochloride, will be used to manipulate these rates, thereby determining the site of action of the drugs and magnitude of their effects. The effectiveness of a beta 2 adrenergic drug, which speeds up mucociliary transport, will also be investigated in patients with respiratory diseases, since transport rates in the three regions will be almost certainly different from those in healthy populations. Transport rates in airways at all levels of the tracheobronchial tree will be computed, using a model for mucociliary clearance based on the asymmetric anatomical model of Horsfield et al.